PROJECT SUMMARY/ABSTRACT For years, the University of Texas Southwestern Medical Center (UTSW) has provided key leadership within the National Clinical Trials Network (NCTN). The leaders of this UG1 application and other faculty members hold major NCTN roles, including chairing clinical trials and committees. From March 2014 through August 2017, UTSW enrolled 520 patients on adult NCTN trials across 13 disease categories. During that time, UTSW faculty authored or co-authored 27 publications directly related to NCTN trials, and have chaired, co-chaired, or served as cooperative group committee chairs on 13 cooperative group trials. Substantial recent growth positions UTSW to expand accrual and scientific contributions. After receiving initial NCI designation in 2010, the Harold C. Simmons Cancer Center received comprehensive designation in 2015. Since 2015, two new hospitals affiliated with UTSW have been constructed. We have a vibrant drug discovery program; SPORE grants in lung cancer and kidney cancer; an Advanced Imaging Research Center; and a Patient Centered Outcomes Research (PCOR) Center. As the only academic medical center and medical school in the Dallas/Ft. Worth (DFW) Metroplex (population 7.2 million) and the only NCI-designated Comprehensive Cancer Center in North Texas, UTSW reaches a large and diverse population that otherwise would not have access to NCTN trials. In recent years, up to 29% of our patients enrolled on NCTN clinical studies were Hispanic, and up to 21% were African American. The specific aims of the UTSW UG1 are the following: Aim 1. Contribute to NCTN trial accrual. We will continue to enroll patients with diverse ethnic and racial backgrounds on therapeutic and non-therapeutic trials. Aim 2. Contribute to NCTN scientific direction. We will bring UTSW basic, translational, and imaging research into hypothesis-driven clinical trials. Aim 3. Provide NCTN leadership. UTSW faculty will continue to chair and co-chair clinical trials and committees in the various NCTN groups, and by participate in NCI activities and initiatives. Aim 4. Promote career development of junior faculty and trainees. UTSW faculty will provide mentoring and guidance in the NCTN. Aim 5. Support NCTN administrative efforts. UTSW faculty will continue to serve on NCTN and NCI regulatory and auditing committees. At multiple steps, the design and conduct of cancer clinical research has become more challenging. Financial pressures have limited the protected time of clinical investigators nationwide. Increasing cost and complexity of clinical trials has prolonged activation timelines and restricted eligibility. UTSW is poised to meet and overcome these challenges. With designated funding and mentoring programs, we continue to develop clinical investigators and disease experts. We have capitalized on a large and diverse patient base, as well as growing bioinformatics capabilities, to optimize the identification, screening, and enrollment of clinical trial subjects. Together, these approaches position UTSW to continue to help lead and expand NCTN efforts.